US Secretary of Defence slammed Venezuela's President Nicolas Maduro on Saturday as an "irresponsible despot" who will "have to go." 

"Ultimately this regime is going to have to go," Mattis said at the Reagan National Defense Forum in California, though he did not suggest the United States would play any role in its removal.

Mattis instead placed responsibility on the Venezuelan people and Latin American states to "help expedite" the end of Maduro's rule "and bring that country back to a more prosperous and positive future." 

"I think what we should do is work by, with and through our Latin American allies as we stabilize this situation," he added.

The South American country has become increasingly isolated amid international criticism of the Maduro regime and an exodus of millions of Venezuelans into neighbouring countries.

The US last year called Maduro a dictator and placed him on a blacklist of leaders that includes Syria's President Bashar al-Assad and North Korea's Kim Jong Un, after he claimed victory in an election widely condemned as a power grab.